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This study assessed the ability of seven children to accurately judge relative durations of auditory and visual stimuli before and after participation in a language remediation program. The goal of the intervention program is to improve the children's ability to detect and identify rapidly changing auditory stimuli, and thereby improve their language-related skills. Children showed improved accuracy on a test of auditory duration judgement following the intervention without analogous improvements in the visual domain, supporting the assertion that intensive training with modified speech improves auditory temporal discrimination. However, these improvements did not generalize to reading skills, as assessed by standard measures of phonological awareness and non-word reading. [ABSTRACT FROM AUTHOR]

Background: Reading and math constitute important academic skills, and as such, reading disability (RD or developmental dyslexia) and math disability (MD or developmental dyscalculia) can have negative consequences for children's educational progress. Although RD and MD are different learning disabilities, they frequently co-occur. Separate theories have implicated the cerebellum and its cortical connections in RD and in MD, suggesting that children with combined reading and math disability (RD + MD) may have altered cerebellar function and disrupted functional connectivity between the cerebellum and cortex during reading and during arithmetic processing., Methods: Here we compared Control and RD + MD groups during a reading task as well as during an arithmetic task on (i) activation of the cerebellum, (ii) background functional connectivity, and (iii) task-dependent functional connectivity between the cerebellum and the cortex., Results: The two groups (Control, RD + MD) did not differ for either task (reading, arithmetic) on any of the three measures (activation, background functional connectivity, task-dependent functional connectivity)., Conclusion: These results do not support theories that children's deficits in reading and math originate in the cerebellum., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Ashburn, Matejko and Eden.)

Meta-analyses on reading show cerebellar activation in adults, but not children, suggesting a possible age-dependent role of the cerebellum in reading. However, the few studies that compare adults and children during reading report mixed cerebellar activation results. Here, we studied (i) cerebellar activation during implicit word processing in adults and children and (ii) functional connectivity (FC) between the cerebellum and left cortical regions involved in reading. First, both groups activated bilateral cerebellum for word processing when compared to fixation, but not when compared to the active control. There were no differences between adults and children. Second, we found intrinsic FC between several cerebellar seed regions and cortical target regions in adults and children, as well as between-group differences. However, task-modulated FC specific to word processing revealed no within- nor between-group results. Together this study does not provide support for a role of the cerebellum in word processing at either age., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Introduction: Developmental dyslexia is a language-based reading disability, yet some have reported motor impairments, usually attributed to cerebellar dysfunction., Methods: Using fMRI, we compared children with and without dyslexia during irregularly paced, left or right-hand finger tapping. Next, we examined seed-to-voxel intrinsic functional connectivity (iFC) using six seed regions of the motor system (left and right anterior lobe of the cerebellum, SM1 and SMA)., Results: A whole-brain task-evoked analysis revealed relatively less activation in the group with dyslexia in right anterior cerebellum during right hand tapping. For iFC, we found the group with dyslexia to have greater iFC between the right SM1 seed and a medial aspect of right postcentral gyrus for left hand tapping; and greater iFC between the left SM1 seed and left thalamus, as well as weaker local iFC around the left SM1 seed region for right hand tapping. Lastly, extracted activity and connectivity values that had been identified in these between-group comparisons were not correlated with measures of reading., Discussion: We conclude that there are some aberrations in motor system function in children with dyslexia, but these are not tied to reading ability., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Turesky, Luetje and Eden.)

Phonological processing skills have not only been shown to be important for reading skills, but also for arithmetic skills. Specifically, previous research in typically developing children has suggested that phonological processing skills may be more closely related to arithmetic problems that are solved through fact retrieval (e.g., remembering the solution from memory) than procedural computation (e.g., counting). However, the relationship between phonological processing and arithmetic in children with learning disabilities (LDs) has not been investigated. Yet, understanding these relationships in children with LDs is especially important because it can help elucidate the cognitive underpinnings of math difficulties, explain why reading and math disabilities frequently co-occur, and provide information on which cognitive skills to target for interventions. In 63 children with LDs, we examined the relationship between different phonological processing skills (phonemic awareness, phonological memory, and rapid serial naming) and arithmetic. We distinguished between arithmetic problems that tend to be solved with fact retrieval versus procedural computation to determine whether phonological processing skills are differentially related to these two arithmetic processes. We found that phonemic awareness, but not phonological memory or rapid serial naming, was related to arithmetic fact retrieval. We also found no association between any phonological processing skills and procedural computation. These results converge with prior research in typically developing children and suggest that phonemic awareness is also related to arithmetic fact retrieval in children with LD. These results raise the possibility that phonemic awareness training might improve both reading and arithmetic fact retrieval skills. RESEARCH HIGHLIGHTS: Relationships between phonological processing and various arithmetic skills were investigated in children with learning disabilities (LDs) for the first time. We found phonemic awareness was related to arithmetic involving fact retrieval, but not to arithmetic involving procedural computation in LDs. The results suggest that phonemic awareness is not only important to skilled reading, but also to some aspects of arithmetic. These results raise the question of whether intervention in phonemic awareness might improve arithmetic fact retrieval skills., (© 2022 The Authors. Developmental Science published by John Wiley & Sons Ltd.)

Gray matter has been shown to be greater in early bilingual adults relative to monolingual adults in regions associated with language (Mechelli et al., 2004), and executive control (EC; Olulade et al., 2016). It is not known, however, if language experience-dependent differences in gray matter volume (GMV) exist in children. Further, any such differences are likely not to be the same as those observed in early bilingual adults, as children have had relatively shorter duration of dual-language exposure and/or less development of brain regions serving EC. We tested these predictions by comparing GMV in Spanish-English early bilingual and English monolingual children, and Spanish-English early bilingual and English monolingual adults (n = 122). Comparing only children revealed relatively more GMV in the bilinguals in bilateral frontal, right inferior frontal, and right superior parietal cortices (regions associated with EC). Bilinguals, however, had less GMV in left inferior parietal cortex (region associated with language). An ANOVA including these children with bilingual and monolingual adults revealed interactions of Language Background by Age Group. There were no regions of more GMV in bilinguals relative to monolinguals that were less pronounced in children than adults, despite the children's shorter dual-language experience. There were relative differences between bilingual and monolingual children that were more pronounced than those in adults in left precentral gyrus and right superior parietal lobule (close to, but not directly in areas associated with EC). Together, early bilingual children manifest relative differences in GMV, and, surprisingly, these do not diverge much from those observed in studies of bilingual adults., (© 2022 The Authors. Human Brain Mapping published by Wiley Periodicals LLC.)

Skilled reading is important in daily life. While the understanding of the neurofunctional organization of this uniquely human skill has advanced significantly, it does not take into consideration the common bilingual experiences around the world. To examine the role of early bilingualism on the neural substrates supporting English word processing, we compared brain activity, as well as functional connectivity, in Spanish-English early bilingual adults (N = 25) and English monolingual adults (N = 33) during single-word processing. Activation analysis revealed no significant differences between the two groups. A seed-to-voxel analysis using eight a priori selected seed-regions (placed in regions known to be involved in reading) revealed relatively stronger functional connectivity in bilinguals between two sets of regions: left superior temporal gyrus seed positively with left lingual gyrus and left middle frontal gyrus seed negatively with left anterior cingulate cortex. Together these results suggest that an early Spanish-English bilingual experience does not modulate local brain activity for English word reading. It does, however, have some influence on the functional intercommunication between brain regions during reading, specifically in two regions associated with reading, which are functionally connected to those inside and outside of the reading network. We conclude that brain regions involved in processing English words are not that different in Spanish-English early bilingual adults relative to monolingual adult users of English., (© 2022 The Authors. Human Brain Mapping published by Wiley Periodicals LLC.)

Studies of reading intervention in dyslexia have shown changes in performance and in brain function. However, there is little consistency in the location of brain regions associated with successful reading gains in children, most likely due to variability/limitations in methodologies (study design, participant criteria, and neuroimaging procedures). Ultimately for the results to be meaningful, the intervention has to be successful, be assessed against a control, use rigorous statistics, and take biological variables (sex) into consideration. Using a randomized, crossover design, 31 children with dyslexia were assigned to a phonological- and orthographic-based tutoring period as well as a within-subjects control period to examine: (1) intervention-induced changes in behavior (reading performance) and in brain activity (during reading); and (2) behavioral and brain activity pre-intervention data that predicted intervention-induced gains in reading performance. We found gains in reading ability following the intervention, but not following the control period, with no effect of participants' sex. However, there were no changes in brain activity following the intervention (regardless of sex), suggesting that individual brain changes are too variable to be captured at the group level. Reading gains were not predicted by pre-intervention behavioral data, but were predicted by pre-intervention brain activity in bilateral supramarginal/angular gyri. Notably, some of this prediction was only found in females. Our results highlight the limitations of brain imaging in detecting the neural correlates of reading intervention in this age group, while providing further evidence for its utility in assessing eventual success of intervention, especially if sex is taken into consideration., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Krafnick, Napoliello, Flowers and Eden.)

Math disability (MD) or developmental dyscalculia is a highly prevalent learning disability involving deficits in computation and arithmetic fact retrieval and is associated with dysfunction of parietal and prefrontal cortices. It has been suggested that dyscalculia (and other learning disabilities and developmental disorders) can be viewed in terms of a broader 'dorsal stream vulnerability,' which could explain a range of dorsal visual stream function deficits, including poor coherent visual motion perception. Behavioral evidence from two studies in typical children has linked performance on visual motion perception to math ability, and a third behavioral study reported poorer visual motion perception in a small group of children with MD compared to controls. Visual motion perception relies on the magnocellular-dominated dorsal stream, particularly its constituent area V5/MT. Here we used functional MRI to measure brain activity in area V5/MT during coherent visual motion processing to test its relationship with math ability. While we found bilateral activation in V5/MT in 66 children/adolescents with varied math abilities, we found no relationships between V5/MT activity and standardized math measures. Next, we selected a group of children/adolescents with MD (n = 23) and compared them to typically developing controls (n = 18), but found no differences in activity in V5/MT or elsewhere in the brain. We followed these frequentist statistics with Bayesian analyses, which favored null models in both studies. We conclude that dorsal stream function subserving visual motion processing in area V5/MT is not related to math ability, nor is it altered in those with the math disability dyscalculia., (Copyright © 2022 The Authors. Published by Elsevier Inc. All rights reserved.)

Prior studies on the brain bases of arithmetic have not focused on (or even described) their participants' language backgrounds. Yet, unlike monolinguals, early bilinguals have the capacity to solve arithmetic problems in both of their two languages. This raises the question whether this ability, or any other experience that comes with being bilingual, affects brain activity for arithmetic in bilinguals relative to monolinguals. Here, we used functional magnetic resonance imaging to compare brain activity in 44 English monolinguals and 44 Spanish-English early bilinguals, during the solving of arithmetic problems in English. We used a factorial design to test for a main effect of bilingual Language Experience. Based on the known modulating roles of arithmetic operation and age, we used two arithmetic tasks (addition and subtraction) and studied two age groups (adults and children). When collapsing across operations and age, we found broad bilateral activation for arithmetic in both the monolingual group and the bilingual group. However, an analysis of variance revealed that there was no effect of Language Experience, nor an interaction of Language Experience with Operation or Age Group. Bayesian analyses within regions of interest chosen for their role in arithmetic further supported the finding of no effect of Language Experience on brain activity underlying arithmetic. We conclude that early bilingualism does not influence the functional neuroanatomy of simple arithmetic., (© 2021 The Authors. Human Brain Mapping published by Wiley Periodicals LLC.)

Behavioral and brain imaging studies speak to commonalities between reading and math. Here, we investigated relationships between individual differences in reading and math ability (single word reading and calculation) with brain anatomy (cortical thickness and surface area) in 342 participants between 6-22 years of age from the NIH Pediatric MRI Database. We found no brain-behavioral correlations in the full sample. When dividing the dataset into three age-specific subgroups, cortical thickness of the left supramarginal gyrus (SMG) and fusiform gyrus (FG) correlated with reading ability in the oldest subgroup (15-22 years) only. Next, we tested unique contributions of these educational measures to neuroanatomy. Single word reading ability, age, and their interaction all contributed unique variance to cortical thickness in the left SMG and intraparietal sulcus (IPS). Age, and the interaction between age and reading, predicted cortical thickness in the left FG. However, regression analyses for math ability showed no relationships with cortical thickness; nor for math or reading ability with surface area. Overall, our results demonstrate relationships between cortical thickness and reading ability in emerging adults, but not in younger age groups. Surprisingly, there were no such relationships with math, and hence no convergence between the reading and math results., (Copyright © 2020 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Reading relies on a left-lateralized brain system, including occipito-temporal (OTC), temporo-parietal, and inferior frontal (IFC) cortices. Neuroimaging studies have investigated whether activation in these cortices is modulated by a language's orthographic depth (consistency of grapheme-to-phoneme conversion). In Spanish-English bilinguals, some but not all studies have reported activation differences between the two languages during reading. Here, we studied Spanish-English early bilingual adults living in the United States (N = 25; 17 females, 8 males). We examined local activity, functional connectivity, and spatially distributed activity patterns during English and Spanish word reading. We found overlap in local activity for the two languages in the left IFC, but no differences in activation between them and few differences in functional connectivity (none of which were in pairs of regions known to be involved in reading); yet, there were spatially distributed patterns of brain activity that differentiate English and Spanish in regions of bilateral cerebellum/left OTC, the left superior occipital gyrus, the left IFC, and the left medial frontal gyrus. Overall, we found no evidence for differences in local activation or functional connectivity during English versus Spanish word processing in regions known to be involved in reading, yet we found brain-based evidence that Spanish-English bilinguals distinguish between the two languages., (Copyright © 2019 Elsevier Inc. All rights reserved.)

The cerebellar deficit hypothesis of dyslexia posits that dysfunction of the cerebellum is the underlying cause for reading difficulties observed in this common learning disability. The present study used functional magnetic resonance imaging (fMRI) and a single word processing task to test for differences in activity and connectivity in children with (n = 23) and without (n = 23) dyslexia. We found cerebellar activity in the control group when word processing was compared to fixation, but not when it was compared to the active baseline task designed to reveal activity specific to reading. In the group with dyslexia there was no cerebellar activity for either contrasts and there were no differences when they were compared to children without dyslexia. Turning to functional connectivity (FC) in the controls, background FC (i.e., not specific to reading) was predominately found between the cerebellum and the occipitaltemporal cortex. In the group with dyslexia, there was background FC between the cerebellum and several cortical regions. When comparing the two groups, they differed in background FC in connections between the seed region right crus I and three left-hemisphere perisylvian target regions. However, there was no task-specific FC for word processing in either group and no between-group differences. Together the results do not support the theory that the cerebellum is affected functionally during reading in children with dyslexia., (© 2019 The Authors. Human Brain Mapping published by Wiley Periodicals, Inc.)

Typical readers rely on two brain pathways for word processing in the left hemisphere: temporo-parietal cortex (TPC) and inferior frontal cortex (IFC), thought to subserve phonological decoding, and occipito-temporal cortex (OTC), including the "visual word form area" (VWFA), thought to subserve orthographic processing. How these regions are affected in developmental dyslexia has been a topic of intense research. We employed fMRI rapid adaptation (fMRI-RA) in adults with low reading skills to examine in independently-defined functional regions of interest (ROIs) phonological selectivity to written words in left TPC and IFC, and to orthographic selectivity to written words in OTC. Consistent with the phonological deficit hypothesis of dyslexia, we found responsivity but not selectivity to phonology, as accessed by written words, in the posterior superior temporal gyrus (pSTG) of the TPC. On the other hand, we found orthographic selectivity in the VWFA of the OTC. We also found selectivity to orthographic and not phonological processing in the IFG, a finding previously reported for typical readers. Together our results demonstrate that in adults with poor reading skills, selectivity to phonology is compromised in pSTG, while selectivity to orthography in the VWFA remains unaffected at this level of processing., (Copyright © 2019. Published by Elsevier Inc.)

Reading is explicitly taught and foreshadows academic and vocational success. Studies comparing typical readers to those with developmental dyslexia have identified anatomical brain differences in bilateral temporo-parietal cortex, left temporo-occipital cortex, and bilateral cerebellum. Yet, it is unclear whether linear relationships exist between these brain structures and single real word reading ability in the general population. If dyslexia represents the lower end of the normal continuum, then relationships between gray matter volume (GMV) and reading ability would exist for all reading levels. Our study examined this question using voxel-based morphometry in a large sample (n = 404) of typically developing participants aged 6-22 derived from the NIH normative database. We tested correlations between individual GMV and single word reading and found none. After dividing this sample into groups based on age and on sex, we only found results in the group aged 15-22: positive correlations between GMV in left fusiform gyrus and reading, driven by females; and in right superior temporal gyrus in males. Multiple regressions also yielded no results, demonstrating that there is no general linear relationship between GMV and single real word reading ability. This provides an important context by which to interpret findings of GMV differences in dyslexia., (Copyright © 2019 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Functional brain imaging studies have characterized the neural bases of voluntary movement for finger tapping in adults, but equivalent information for children is lacking. When contrasted to adults, one would expect children to have relatively greater activation, reflecting compensation for an underdeveloped motor system combined with less experience in the execution of voluntary movement. To test this hypothesis, we acquired functional magnetic resonance imaging (fMRI) data on 17 healthy right-handed children (7.48 ± 0.66 years) and 15 adults (24.9 ± 2.9 years) while they performed an irregularly paced finger-tapping task in response to a visual cue (left- and right-hand examined separately). Whole-brain within-group analyses revealed that finger tapping in either age group and for either hand activated contralateral SM1, SMA, ipsilateral anterior cerebellum, and occipital cortices. We used an ANOVA factorial design to test for main effects of Age Group (children vs adults), Hand (left vs. right), and their interactions. For main effects of Age Group, children showed relatively greater activity in left SM1 (extending into bilateral SMA), and, surprisingly, adults exhibited relatively greater activity in right pre-SMA/SMA (extending into left pre-SMA/SMA), right lateral globus pallidus, left putamen, and right anterior cerebellum. The interaction of Age Group × Hand revealed that while both groups activated right SM1 during left finger tapping and exhibited signal decreases (i.e., below fixation baseline) during right finger tapping, both these responses were attenuated in children relative to adults. These data provide an important foundation by which to study children with motor disorders., (© 2018 Wiley Periodicals, Inc.)

There is a large corpus of brain imaging studies examining the dorsal visual pathway, especially area V5/MT during visual motion perception. However, despite evidence suggesting a protracted development of the dorsal visual stream, and a role of this pathway in neurodevelopmental disorders, V5/MT has not been characterized developmentally. Further, experiential factors such as reading acquisition may play a modulating role in any age-dependent changes. Here we used a coherent visual motion detection task to examine V5/MT activity and connectivity in typical participants in two studies: a Cross- Sectional Study comparing adults and children; and a Longitudinal Study of 2nd graders followed into 3rd grade. In the Cross-Sectional Study, a whole-brain analysis revealed no differences between the two groups, whereas a region of interest (ROI) approach identified greater activation in left (right trending) V5/MT in adults compared to children. However, when we measured V5/MT activation individually for each participant, children and adults showed no difference in the location or intensity of activation, although children did exhibit relatively larger extent of V5/MT activation bilaterally. There was also relatively greater functional connectivity in the children between left and right occipitotemporal cortex, including V5/MT. The Longitudinal Study revealed no changes in V5/MT activation for any measures of activation or functional connectivity from 2nd to 3rd grade. Finally, there was no evidence of an association between reading and V5/MT over time, nor predictive power of V5/MT activity for later reading. Together, our results indicate similar V5/MT activity across age groups, with relatively greater extent of V5/MT activation and functional connectivity in children relative to adults, bilaterally. These differences were not apparent over the time course of one year, suggesting that these developmental changes occur over a more protracted period., (Copyright © 2018 Elsevier Inc. All rights reserved.)

A central question in the study of the neural basis of written language is whether reading and spelling utilize shared orthographic representations. While recent studies employing fMRI to test this question report that the left inferior frontal gyrus (IFG) and ventral occipitotemporal cortex (vOTC) are active during both spelling and reading in the same subjects (Purcell et al., 2011a; Rapp and Lipka, 2011), the spatial resolution of fMRI limits the interpretation of these findings. Specifically, it is unknown if the neurons which encode orthography for reading are also involved in spelling of the same words. Here we address this question by employing an event-related functional magnetic resonance imaging-adaptation (fMRI-A) paradigm designed to examine shared orthographic representations across spelling and reading. First, we identified areas that independently showed adaptation to reading, and adaptation to spelling. Then we identified spatial convergence for these two separate maps via a conjunction analysis. Consistent with previous studies (Purcell et al., 2011a; Rapp and Lipka, 2011), this analysis revealed the left dorsal IFG, vOTC and supplementary motor area. To further validate these observations, we then interrogated these regions using an across-task adaptation technique, and found adaptation across reading and spelling in the left dorsal IFG (BA 44/9). Our final analysis focused specifically on the Visual Word Form Area (VWFA) in the vOTC, whose variability in location among subjects requires the use of subject-specific identification mechanisms (Glezer and Riesenhuber, 2013). Using a functional localizer for reading, we defined the VWFA in each subject, and found adaptation effects for both within the spelling and reading conditions, respectively, as well as across spelling and reading. Because none of these effects were observed during a phonological/semantic control condition, we conclude that the left dorsal IFG and VWFA are involved in accessing the same orthography-specific representations for spelling and reading., (Copyright © 2016 Elsevier Inc. All rights reserved.)

Arithmetic and written language are uniquely human skills acquired during early schooling and used daily. While prior studies have independently characterized the neural bases for arithmetic and reading, here we examine both skills in a single study to capture their shared and unique cognitive mechanisms, as well as the role of age/experience in modulating their neural representations. We used functional MRI in 7- to 29-year-olds who performed single-digit subtraction, single-digit addition, and single-word reading. Using a factorial design, we examined the main effects of Task (subtraction, addition, reading) and Age (as a continuous variable), and their interactions. A main effect of Task revealed preferential activation for subtraction in bilateral intraparietal sulci and supramarginal gyri, right insula, inferior frontal gyrus, and cingulate. The right middle temporal gyrus and left superior temporal gyrus were preferentially active for both addition and reading, and left fusiform gyrus was preferentially active for reading. A main effect of Age revealed increased activity in older participants in right angular gyrus, superior temporal sulcus, and putamen, and less activity in left supplementary motor area, suggesting a left frontal to right temporo-parietal shift of activity with increasing age/experience across all tasks. Interactions for Task by Age were found in right hippocampus and left middle frontal gyrus, with older age invoking greater activity for addition and at the same time less activity for subtraction and reading. Together, in a study conducted in the same participants using similar task and acquisition parameters, the results reveal the neural substrates of these educationally relevant cognitive skills in typical participants in the context of age/experience., (Copyright © 2016 Elsevier Inc. All rights reserved.)

The functional neuroanatomy of finger movements has been characterized with neuroimaging in young adults. However, less is known about the aging motor system. Several studies have contrasted movement-related activity in older versus young adults, but there is inconsistency among their findings. To address this, we conducted an activation likelihood estimation (ALE) meta-analysis on within-group data from older adults and young adults performing regularly paced right-hand finger movement tasks in response to external stimuli. We hypothesized that older adults would show a greater likelihood of activation in right cortical motor areas (i.e., ipsilateral to the side of movement) compared to young adults. ALE maps were examined for conjunction and between-group differences. Older adults showed overlapping likelihoods of activation with young adults in left primary sensorimotor cortex (SM1), bilateral supplementary motor area, bilateral insula, left thalamus, and right anterior cerebellum. Their ALE map differed from that of the young adults in right SM1 (extending into dorsal premotor cortex), right supramarginal gyrus, medial premotor cortex, and right posterior cerebellum. The finding that older adults uniquely use ipsilateral regions for right-hand finger movements and show age-dependent modulations in regions recruited by both age groups provides a foundation by which to understand age-related motor decline and motor disorders.

The "bilingual advantage" theory stipulates that constant selection and suppression between 2 languages results in enhanced executive control (EC). Behavioral studies of EC in bilinguals have employed wide-ranging tasks and report some conflicting results. To avoid concerns about tasks, we employed a different approach, measuring gray matter volume (GMV) in adult bilinguals, reasoning that any EC-associated benefits should manifest as relatively greater frontal GMV. Indeed, Spanish-English-speaking bilinguals exhibited greater bilateral frontal GMV compared with English-speaking monolinguals. Was this observation attributable to the constant selection and inhibition of 2 spoken languages? To answer this question, we drew on bimodal bilinguals of American Sign Language (ASL) and English who, unlike unimodal bilinguals, can simultaneously use both languages and have been shown not to possess the EC advantage. In this group, there was no greater GMV when compared with monolinguals. Together these results provide neuroanatomical evidence in support of the bilingual advantage theory., (© The Author 2015. Published by Oxford University Press. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.)

Learning to read is thought to involve the recruitment of left hemisphere ventral occipitotemporal cortex (OTC) by a process of "neuronal recycling", whereby object processing mechanisms are co-opted for reading. Under the same theoretical framework, it has been proposed that the visual word form area (VWFA) within OTC processes orthographic stimuli independent of culture and writing systems, suggesting that it is universally involved in written language. However, this "script invariance" has yet to be demonstrated in monolingual readers of two different writing systems studied under the same experimental conditions. Here, using functional magnetic resonance imaging (fMRI), we examined activity in response to English Words and Chinese Characters in 1st graders in the United States and China, respectively. We examined each group separately and found the readers of English as well as the readers of Chinese to activate the left ventral OTC for their respective native writing systems (using both a whole-brain and a bilateral OTC-restricted analysis). Critically, a conjunction analysis of the two groups revealed significant overlap between them for native writing system processing, located in the VWFA and therefore supporting the hypothesis of script invariance. In the second part of the study, we further examined the left OTC region responsive to each group's native writing system and found that it responded equally to Object stimuli (line drawings) in the Chinese-reading children. In English-reading children, the OTC responded much more to Objects than to English Words. Together, these results support the script invariant role of the VWFA and also support the idea that the areas recruited for character or word processing are rooted in object processing mechanisms of the left OTC., (Copyright © 2016 Elsevier Inc. All rights reserved.)

fMRI studies using a region-of-interest approach have revealed that the ventral portion of the left occipito-temporal cortex, which is specialized for orthographic processing of visually presented words (and includes the so-called "visual word form area", VWFA), is characterized by a posterior-to-anterior gradient of increasing selectivity for words in typically reading adults, adolescents, and children (e.g. Brem et al., 2006, 2009). Similarly, the left inferior frontal cortex (IFC) has been shown to exhibit a medial-to-lateral gradient of print selectivity in typically reading adults (Vinckier et al., 2007). Functional brain imaging studies of dyslexia have reported relative underactivity in left hemisphere occipito-temporal and inferior frontal regions using whole-brain analyses during word processing tasks. Hence, the question arises whether gradient sensitivities in these regions are altered in dyslexia. Indeed, a region-of-interest analysis revealed the gradient-specific functional specialization in the occipito-temporal cortex to be disrupted in dyslexic children (van der Mark et al., 2009). Building on these studies, we here (1) investigate if a word-selective gradient exists in the inferior frontal cortex in addition to the occipito-temporal cortex in normally reading children, (2) compare typically reading with dyslexic children, and (3) examine functional connections between these regions in both groups. We replicated the previously reported anterior-to-posterior gradient of increasing selectivity for words in the left occipito-temporal cortex in typically reading children, and its absence in the dyslexic children. Our novel finding is the detection of a pattern of increasing selectivity for words along the medial-to-lateral axis of the left inferior frontal cortex in typically reading children and evidence of functional connectivity between the most lateral aspect of this area and the anterior aspects of the occipito-temporal cortex. We report absence of an IFC gradient and connectivity between the lateral aspect of the IFC and the anterior occipito-temporal cortex in the dyslexic children. Together, our results provide insights into the source of the anomalies reported in previous studies of dyslexia and add to the growing evidence of an orthographic role of IFC in reading.

Some arithmetic procedures, such as addition of small numbers, rely on fact retrieval mechanisms supported by left hemisphere perisylvian language areas, while others, such as subtraction, rely on procedural-based mechanisms subserved by bilateral parietal cortices. Previous work suggests that developmental dyslexia, a reading disability, is accompanied by subtle deficits in retrieval-based arithmetic, possibly because of compromised left hemisphere function. To test this prediction, we compared brain activity underlying arithmetic problem solving in children with and without dyslexia during addition and subtraction operations using a factorial design. The main effect of arithmetic operation (addition versus subtraction) for both groups combined revealed activity during addition in the left superior temporal gyrus and activity during subtraction in the bilateral intraparietal sulcus, the right supramarginal gyrus and the anterior cingulate, consistent with prior studies. For the main effect of diagnostic group (dyslexics versus controls), we found less activity in dyslexic children in the left supramarginal gyrus. Finally, the interaction analysis revealed that while the control group showed a strong response in the right supramarginal gyrus for subtraction but not for addition, the dyslexic group engaged this region for both operations. This provides physiological evidence in support of the theory that children with dyslexia, because of disruption to left hemisphere language areas, use a less optimal route for retrieval-based arithmetic, engaging right hemisphere parietal regions typically used by good readers for procedural-based arithmetic. Our results highlight the importance of language processing for mathematical processing and illustrate that children with dyslexia have impairments that extend beyond reading., (Copyright © 2014 Elsevier Inc. All rights reserved.)

Developmental dyslexia, characterized by unexpected reading difficulty, is associated with anomalous brain anatomy and function. Previous structural neuroimaging studies have converged in reports of less gray matter volume (GMV) in dyslexics within left hemisphere regions known to subserve language. Due to the higher prevalence of dyslexia in males, these studies are heavily weighted towards males, raising the question whether studies of dyslexia in females only and using the same techniques, would generate the same findings. In a replication study of men, we obtained the same findings of less GMV in dyslexics in left middle/inferior temporal gyri and right postcentral/supramarginal gyri as reported in the literature. However, comparisons in women with and without dyslexia did not yield left hemisphere differences, and instead, we found less GMV in right precuneus and paracentral lobule/medial frontal gyrus. In boys, we found less GMV in left inferior parietal cortex (supramarginal/angular gyri), again consistent with previous work, while in girls differences were within right central sulcus, spanning adjacent gyri, and left primary visual cortex. Our investigation into anatomical variants in dyslexia replicates existing studies in males, but at the same time shows that dyslexia in females is not characterized by involvement of left hemisphere language regions but rather early sensory and motor cortices (i.e., motor and premotor cortex, primary visual cortex). Our findings suggest that models on the brain basis of dyslexia, primarily developed through the study of males, may not be appropriate for females and suggest a need for more sex-specific investigations into dyslexia.

The study of congenitally deaf adult humans provides an opportunity to examine neuroanatomical plasticity resulting from altered sensory experience. However, attributing the source of the brain's structural variance in the deaf is complicated by the fact that deaf individuals also differ in their language experiences (e.g., sign vs spoken), which likely influence brain anatomy independently. Although the majority of deaf individuals in the United States are born to hearing parents and are exposed to English, not American Sign Language (ASL) as their first language, most studies on deafness have been conducted with deaf native users of ASL (deaf signers). This raises the question of whether observations made in deaf signers can be generalized. Using a factorial design, we compared gray (GMV) and white (WMV) matter volume in deaf and hearing native users of ASL, as well as deaf and hearing native users of English. Main effects analysis of sensory experience revealed less GMV in the deaf groups combined (compared with hearing groups combined) in early visual areas and less WMV in a left early auditory region. The interaction of sensory experience and language experience revealed that deaf native users of English had fewer areas of anatomical differences than did deaf native users of ASL (each compared with their hearing counterparts). For deaf users of ASL specifically, WMV differences resided in language areas such as the left superior temporal and inferior frontal regions. Our results demonstrate that cortical plasticity resulting from deafness depends on language experience and that findings from native signers cannot be generalized.

Studies have converged in their findings of relatively less gray matter volume (GMV) in developmental dyslexia in bilateral temporoparietal and left occipitotemporal cortical regions. However, the interpretation of these results has been difficult. The reported neuroanatomical differences in dyslexia may be causal to the reading problems, following from, for example, neural migration errors that occurred during early human development and before learning to read. Alternatively, less GMV may represent the consequence of an impoverished reading experience, akin to the experience-dependent GMV differences attributed to illiterate compared with literate adults. Most likely, a combination of these factors is driving these observations. Here we attempt to disambiguate these influences by using a reading level-matched design, where dyslexic children were contrasted not only with age-matched controls, but also with younger controls who read at the same level as the dyslexics. Consistent with previous reports, dyslexics showed less GMV in multiple left and right hemisphere regions, including left superior temporal sulcus when compared with age-matched controls. However, not all of these differences emerged when dyslexics were compared with controls matched on reading abilities, with only right precentral gyrus GMV surviving this second analysis. When similar analyses were performed for white matter volume, no regions emerged from both comparisons. These results indicate that the GMV differences in dyslexia reported here and in prior studies are in large part the outcome of experience (e.g., disordered reading experience) compared with controls, with only a fraction of the differences being driven by dyslexia per se.

Developmental dyslexia is a reading disorder, yet deficits also manifest in the magnocellular-dominated dorsal visual system. Uncertainty about whether visual deficits are causal or consequential to reading disability encumbers accurate identification and appropriate treatment of this common learning disability. Using fMRI, we demonstrate in typical readers a relationship between reading ability and activity in area V5/MT during visual motion processing and, as expected, also found lower V5/MT activity for dyslexic children compared to age-matched controls. However, when dyslexics were matched to younger controls on reading ability, no differences emerged, suggesting that weakness in V5/MT may not be causal to dyslexia. To further test for causality, dyslexics underwent a phonological-based reading intervention. Surprisingly, V5/MT activity increased along with intervention-driven reading gains, demonstrating that activity here is mobilized through reading. Our results provide strong evidence that visual magnocellular dysfunction is not causal to dyslexia but may instead be consequential to impoverished reading., (Copyright © 2013 Elsevier Inc. All rights reserved.)

The visual word form system (VWFS), located in the occipito-temporal cortex, is involved in orthographic processing of visually presented words (Cohen et al., 2002). Recent fMRI studies in children and adults have demonstrated a gradient of increasing word-selectivity along the posterior-to-anterior axis of this system (Vinckier et al., 2007), yet whether this pattern is modified by the increased reading experience afforded by age is still in question. In this study, we employed fMRI and an implicit word-processing task, and then used a region of interest analysis approach along the occipito-temporal cortex to test the prediction that the selectivity for words along the extent of the VWFS differs between older experienced and younger novice readers. Our results showed differences between children and adults during word processing in the anterior left occipito-temporal cortex, providing evidence of developmental refinement for word recognition along the VWFS., (Copyright © 2012 Elsevier Inc. All rights reserved.)

Experience-dependent plasticity in deaf participants has been shown in a variety of studies focused on either the dorsal or ventral aspects of the visual system, but both systems have never been investigated in concert. Using functional magnetic resonance imaging (fMRI), we investigated functional plasticity for spatial processing (a dorsal visual pathway function) and for object processing (a ventral visual pathway function) concurrently, in the context of differing sensory (auditory deprivation) and language (use of a signed language) experience. During scanning, deaf native users of American Sign Language (ASL), hearing native ASL users, and hearing participants without ASL experience attended to either the spatial arrangement of frames containing objects or the identity of the objects themselves. These two tasks revealed the expected dorsal/ventral dichotomy for spatial versus object processing in all groups. In addition, the object identity matching task contained both face and house stimuli, allowing us to examine category-selectivity in the ventral pathway in all three participant groups. When contrasting the groups we found that deaf signers differed from the two hearing groups in dorsal pathway parietal regions involved in spatial cognition, suggesting sensory experience-driven plasticity. Group differences in the object processing system indicated that responses in the face-selective right lateral fusiform gyrus and anterior superior temporal cortex were sensitive to a combination of altered sensory and language experience, whereas responses in the amygdala were more closely tied to sensory experience. By selectively engaging the dorsal and ventral visual pathways within participants in groups with different sensory and language experiences, we have demonstrated that these experiences affect the function of both of these systems, and that certain changes are more closely tied to sensory experience, while others are driven by the combination of sensory and language experience., (Copyright © 2011 Elsevier Inc. All rights reserved.)

Brain imaging studies have identified a left-lateralized network of regions that are engaged when monolinguals read. However, for individuals who are native speakers of two languages, it is unclear whether this pattern of activity is maintained across both languages or if it deviates according to language-specific properties. We used functional magnetic resonance imaging to investigate single-word processing in Spanish and in English in 12 proficient early Spanish-English bilinguals matched in skill level in both languages. Word processing in Spanish engaged the left inferior frontal and left middle temporal gyri. Word processing in English activated the left inferior frontal, middle frontal, and fusiform gyri extending to inferior temporal gyrus and the right middle temporal gyrus extending into superior temporal sulcus. The comparison of reading in Spanish greater than reading in English revealed involvement of the left middle temporal gyrus extending into the superior temporal sulcus. English greater than Spanish, however, demonstrated greater engagement of the left middle frontal gyrus extending into the superior frontal gyrus. We conclude that although word processing in either language activates classical areas associated with reading, there are language-specific differences, which can be attributed to the disparity in orthographic transparency. English, an orthographically deep language, may require greater engagement of the frontal regions for phonological coding, whereas Spanish allows increased access to semantic processing via the left middle temporal areas. Together, these results suggest that bilinguals will show adjustments to the typical neural representation of reading as necessitated by the demands of the orthography., (Copyright © 2011 Wiley Periodicals, Inc.)

Producing written words requires "central" cognitive processes (such as orthographic long-term and working memory) as well as more peripheral processes responsible for generating the motor actions needed for producing written words in a variety of formats (handwriting, typing, etc.). In recent years, various functional neuroimaging studies have examined the neural substrates underlying the central and peripheral processes of written word production. This study provides the first quantitative meta-analysis of these studies by applying activation likelihood estimation (ALE) methods (Turkeltaub et al., 2002). For alphabet languages, we identified 11 studies (with a total of 17 experimental contrasts) that had been designed to isolate central and/or peripheral processes of word spelling (total number of participants = 146). Three ALE meta-analyses were carried out. One involved the complete set of 17 contrasts; two others were applied to subsets of contrasts to distinguish the neural substrates of central from peripheral processes. These analyses identified a network of brain regions reliably associated with the central and peripheral processes of word spelling. Among the many significant results, is the finding that the regions with the greatest correspondence across studies were in the left inferior temporal/fusiform gyri and left inferior frontal gyrus. Furthermore, although the angular gyrus (AG) has traditionally been identified as a key site within the written word production network, none of the meta-analyses found it to be a consistent site of activation, identifying instead a region just superior/medial to the left AG in the left posterior intraparietal sulcus. These meta-analyses and the discussion of results provide a valuable foundation upon which future studies that examine the neural basis of written word production can build.

Studies in children and adults with the reading disability developmental dyslexia have shown behavioral improvements after reading intervention. In another line of work, it has been shown that intensive training in a variety of cognitive and sensorimotor skills can result in changes in gray matter volume (GMV). This study examined changes in GMV following intensive reading intervention in children with dyslexia using voxel-based morphometry (VBM). Eleven dyslexic children underwent an eight week training focused on mental imagery, articulation and tracing of letters, groups of letters and words, which resulted in significant gains in reading skills. This was followed by an eight week null period (control) where no intervention was administered and no further significant gains in reading were observed. Structural scans were obtained before the intervention, after the intervention and after the null period. GMV increases between the first two time points were found in the left anterior fusiform gyrus/hippocampus, left precuneus, right hippocampus and right anterior cerebellum. However these areas did not change between time points two and three (control period), suggesting that the changes were specific to the intervention period. These results demonstrate for the first time that (1) training-induced changes in GMV can be observed in a pediatric sample and (2) reading improvements induced by intervention are accompanied by GMV changes., (Copyright © 2010 Elsevier Inc. All rights reserved.)

Neuroplasticity can be defined as the ability of the nervous system to respond to intrinsic or extrinsic stimuli by reorganizing its structure, function and connections. Major advances in the understanding of neuroplasticity have to date yielded few established interventions. To advance the translation of neuroplasticity research towards clinical applications, the National Institutes of Health Blueprint for Neuroscience Research sponsored a workshop in 2009. Basic and clinical researchers in disciplines from central nervous system injury/stroke, mental/addictive disorders, paediatric/developmental disorders and neurodegeneration/ageing identified cardinal examples of neuroplasticity, underlying mechanisms, therapeutic implications and common denominators. Promising therapies that may enhance training-induced cognitive and motor learning, such as brain stimulation and neuropharmacological interventions, were identified, along with questions of how best to use this body of information to reduce human disability. Improved understanding of adaptive mechanisms at every level, from molecules to synapses, to networks, to behaviour, can be gained from iterative collaborations between basic and clinical researchers. Lessons can be gleaned from studying fields related to plasticity, such as development, critical periods, learning and response to disease. Improved means of assessing neuroplasticity in humans, including biomarkers for predicting and monitoring treatment response, are needed. Neuroplasticity occurs with many variations, in many forms, and in many contexts. However, common themes in plasticity that emerge across diverse central nervous system conditions include experience dependence, time sensitivity and the importance of motivation and attention. Integration of information across disciplines should enhance opportunities for the translation of neuroplasticity and circuit retraining research into effective clinical therapies.

In this study we employed a novel technique to examine the neural basis of written spelling by having subjects touch-type single words on an fMRI compatible QWERTY keyboard. Additionally, in the same group of participants we determined if task-related signal changes associated with typed spelling were also co-localized with or separate from those for reading. Of particular interest were the left inferior frontal gyrus, left inferior parietal lobe as well as an area in the left occipitotemporal cortex termed the Visual Word Form Area (VWFA), each of which have been associated with both spelling and reading. Our results revealed that typed spelling was associated with a left hemisphere network of regions which included the inferior frontal gyrus, intraparietal sulcus, inferior temporal/fusiform gyrus, as well as a region in the superior/middle frontal gyrus, near Exner's area. A conjunction analysis of activation associated with spelling and reading revealed a significant overlap in the left inferior frontal gyrus and occipitotemporal cortex. Interestingly, within the occipitotemporal cortex just lateral and superior to the VWFA we identified an area that was selectively associated with spelling, as revealed by a direct comparison of the two tasks. These results demonstrate that typed spelling activates a predominantly left hemisphere network, a subset of which is functionally relevant to both spelling and reading. Further analysis revealed that the left occipitotemporal cortex contains regions with both conjoint and dissociable patterns of activation for spelling and reading., (Published by Elsevier Inc.)

Visual form recognition is mediated by the ventral extrastriate processing stream. Some regions of ventral stream cortex show preferential activity for specific stimulus categories, but little is known about how this regional specialization develops. Acquisition of letter-naming skill is of particular interest because letter recognition serves as the gateway to visual processing of words, and fluent letter naming predicts children's reading success. For this reason, we examined the school-age development of visual letter processing using fMRI. In a 2 x 2 design, we compared ventral stream BOLD activity in two groups, children (n= 22, age 6-11) and adults (n= 15, age 20-22), during two tasks: naming of single letters and naming of simple line drawings of objects. We hypothesized that, based on adults' greater experience with letters, the posterior left fusiform gyrus would be activated more in adults for letter naming than it would be in children. We found that bilateral areas of ventral stream cortex during letter naming were activated in both children and adults and that the midposterior areas of the fusiform gyrus in both hemispheres were activated to a greater degree in adults than in children. There were no areas within the ventral stream in either hemisphere that were activated preferentially for letters over line drawings, nor were there any significant differences in the developmental changes observed for letter naming compared to object naming. These findings indicate that visual processing of single letters continues to develop in both hemispheres during grade school. However, we found no evidence for development of areas specialized for single letter processing. Rather, our findings suggest that letter recognition is performed using the same general form recognition systems as are used to process other visually similar stimuli.

Academic success and occupational outcome rely on a person's ability to attend to and learn from their surroundings. The cognitive mechanisms underlying these respective skills are impaired in individuals with attention deficit hyperactivity disorder (ADHD) and learning disability (LD). The high co-occurrence between ADHD and the learning disability developmental dyslexia has raised the possibility of a common etiology. We propose that studying the functional anatomy of disordered executive control and reading-related skills using carefully selected paradigms, coupled with rigorous studies of intervention efficacy, provide the most promising avenue for ameliorating these two commonly encountered impediments to learning.

Reading and phonological processing deficits have been the primary focus of neuroimaging studies addressing the neurologic basis of developmental dyslexia, but to date there has been no objective assessment of the consistency of these findings. To address this issue, spatial coordinates reported in the literature were submitted to two parallel activation likelihood estimate (ALE) meta-analyses. First, a meta-analysis including 96 foci from nine publications identified regions where typical readers are likely to show greater activation than dyslexics: two left extrastriate areas within BA 37, precuneus, inferior parietal cortex, superior temporal gyrus, thalamus, and left inferior frontal gyrus. Right hemisphere ALE foci representing hypoactivity in dyslexia were found in the fusiform, postcentral, and superior temporal gyri. To identify regions in which dyslexic subjects reliably show greater activation than controls, 75 foci from six papers were entered into a second meta-analysis. Here ALE results revealed hyperactivity associated with dyslexia in right thalamus and anterior insula. These findings suggest that during the performance of a variety of reading tasks, normal readers activate left-sided brain areas more than dyslexic readers do, whereas dyslexia is associated with greater right-sided brain activity. The most robust result was in left extrastriate cortex, where hypoactivity associated with dyslexia was found. However, the ALE maps provided no support for cerebellar dysfunction, nor for hyperactivity in left frontal cortex in dyslexia, suggesting that these findings, unlike those described above, are likely to be more varied in terms of their reproducibility or spatial location.

Previous work in deaf populations on phonological coding and working memory, two skills thought to play an important role in the acquisition of written language skills, have focused primarily on signers or did not clearly identify the subjects' native language and communication mode. In the present study, we examined the effect of sensory experience, early language experience, and communication mode on the phonological awareness skills and serial recall of linguistic items in deaf and hearing individuals of different communicative and linguistic backgrounds: hearing nonsigning controls, hearing users of ASL, deaf users of ASL, deaf oral users of English, and deaf users of cued speech. Since many current measures of phonological awareness skills are inappropriate for deaf populations on account of the verbal demands in the stimuli or response, we devised a nonverbal phonological measure that addresses this limitation. The Phoneme Detection Test revealed that deaf cuers and oral users, but not deaf signers, performed as well as their hearing peers when detecting phonemes not transparent in the orthography. The second focus of the study examined short-term memory skills and found that in response to the traditional digit span as well as an experimental visual version, digit-span performance was similar across the three deaf groups, yet deaf subjects' retrieval was lower than that of hearing subjects. Our results support the claim (Bavelier et al., 2006) that lexical items processed in the visual-spatial modality are not as well retained as information processed in the auditory channel. Together these findings show that the relationship between working memory, phonological coding, and reading may not be as tightly interwoven in deaf students as would have been predicted from work conducted in hearing students.

The current study was conducted to test the premise that computer-based intervention that targets auditory temporal processing combined with language exercises (Fast ForWord) is effective in remediating children with disorders of language and reading. Sixty-five middle school struggling readers were randomly assigned to one of five groups and over a 12-week-period received one of the following interventions: (1) two phases of intervention with Fast ForWord (FFW, experimental group), (2) two phases of intervention with SuccessMaker (SM, active control group), (3) FFW followed by SM, (4) SM followed by FFW, or (5) no intervention beyond the regular class curriculum (developmental control group). Changes in reading, phonemic awareness, spelling and language skills were assessed via a repeated measures MANOVA. Results indicated significant within-subjects effects (i.e., change for all participants over time), but no between-subject group differences, failing to show that Fast ForWord resulted in any gains over and above those seen in the other groups.

Developmental dyslexia is characterized by poor reading ability and impairments on a range of tasks including phonological processing and processing of sensory information. Some recent studies have found deficits in implicit sequence learning using the serial reaction time task, but others have not. Other skills, such as global visuo-spatial processing may even be enhanced in dyslexics, although deficits have also been noted. The present study compared dyslexic and non-dyslexic college students on two implicit learning tasks, an alternating serial response time task in which sequential dependencies exist across non-adjacent elements and a spatial context learning task in which the global configuration of a display cues the location of a search target. Previous evidence indicates that these implicit learning tasks are based on different underlying brain systems, fronto-striatal-cerebellar circuits for sequence learning and medial temporal lobe for spatial context learning. Results revealed a double dissociation: dyslexics showed impaired sequence learning, but superior spatial context learning. Consistent with this group difference, there was a significant positive correlation between reading ability (single real and non-word reading) and sequence learning, but a significant negative correlation between these measures and spatial context learning. Tests of explicit knowledge confirmed that learning was implicit for both groups on both tasks. These findings indicate that dyslexic college students are impaired on some kinds of implicit learning, but not on others. The specific nature of their learning deficit is consistent with reports of physiological and anatomical differences for individuals with dyslexia in frontal and cerebellar structures.

Aloud reading of novel words is achieved by phonological decoding, a process in which grapheme-to-phoneme conversion rules are applied to "sound out" a word's spoken representation. Numerous brain imaging studies have examined the neural bases of phonological decoding by contrasting pseudoword (pronounceable nonwords) to real word reading. However, only a few investigations have examined pseudoword reading under both aloud and silent conditions, task parameters that are likely to significantly alter the functional anatomy of phonological decoding. Subjects participated in an fMRI study of aloud pseudoword, aloud real word, silent pseudoword, and silent real word reading. Using this two-by-two design, we examined effects of word-type (real words vs. pseudowords) and response-modality (silent vs. aloud) and their interactions. We found 1) four regions to be invariantly active across the four reading conditions: the anterior aspect of the left precentral gyrus (Brodmann's Area (BA) 6), and three areas within the left ventral occipitotemporal cortex; 2) a main effect of word-type (pseudowords > words) in left inferior frontal gyrus and left intraparietal sulcus; 3) a main effect of response-modality (aloud > silent) that included bilateral motor, auditory, and extrastriate cortex; and 4) a single left hemisphere extrastriate region showing a word-type by response-modality interaction effect. This region, within the posterior fusiform cortex at BA 19, was uniquely modulated by varying phonological processing demands. This result suggests that when reading, word forms are subject to phonological analysis at the point they are first recognized as alphabetic stimuli and BA 19 is involved in processing the phonological properties of words., (Copyright 2005 Wiley-Liss, Inc.)

Language development entails four fundamental and interactive abilities: listening, speaking, reading, and writing. Over the past four decades, a large body of evidence has indicated that reading acquisition is strongly associated with a child's listening skills, particularly the child's sensitivity to phonological structures of spoken language. Furthermore, it has been hypothesized that the close relationship between reading and listening is manifested universally across languages and that behavioral remediation using strategies addressing phonological awareness alleviates reading difficulties in dyslexics. The prevailing view of the central role of phonological awareness in reading development is largely based on studies using Western (alphabetic) languages, which are based on phonology. The Chinese language provides a unique medium for testing this notion, because logographic characters in Chinese are based on meaning rather than phonology. Here we show that the ability to read Chinese is strongly related to a child's writing skills and that the relationship between phonological awareness and Chinese reading is much weaker than that in reports regarding alphabetic languages. We propose that the role of logograph writing in reading development is mediated by two possibly interacting mechanisms. The first is orthographic awareness, which facilitates the development of coherent, effective links among visual symbols, phonology, and semantics; the second involves the establishment of motor programs that lead to the formation of long-term motor memories of Chinese characters. These findings yield a unique insight into how cognitive systems responsible for reading development and reading disability interact, and they challenge the prominent phonological awareness view.

Brain imaging studies have explored the neural mechanisms of recovery in adults following acquired disorders and, more recently, childhood developmental disorders. However, the neural systems underlying adult rehabilitation of neurobiologically based learning disabilities remain unexplored, despite their high incidence. Here we characterize the differences in brain activity during a phonological manipulation task before and after a behavioral intervention in adults with developmental dyslexia. Phonologically targeted training resulted in performance improvements in tutored compared to nontutored dyslexics, and these gains were associated with signal increases in bilateral parietal and right perisylvian cortices. Our findings demonstrate that behavioral changes in tutored dyslexic adults are associated with (1) increased activity in those left-hemisphere regions engaged by normal readers and (2) compensatory activity in the right perisylvian cortex. Hence, behavioral plasticity in adult developmental dyslexia involves two distinct neural mechanisms, each of which has previously been observed either for remediation of developmental or acquired reading disorders.

Although persuasive behavioral evidence demonstrates the superior dexterity of the right hand in most people under a variety of conditions, little is known about the neural mechanisms responsible for this phenomenon. As this lateralized superiority is most evident during the performance of repetitive, speeded movement, we used parametric rate variations to compare visually paced movement of the right and left hands. Twelve strongly right-handed subjects participated in a functional magnetic resonance imaging (fMRI) experiment involving variable rate thumb movements. For movements of the right hand, contralateral rate-related activity changes were identified in the precentral gyrus, thalamus, and posterior putamen. For left-hand movements, activity was seen only in the contralateral precentral gyrus, consistent with the existence of a rate-sensitive motor control subsystem involving the left, but not the right, medial premotor corticostriatal loop in right-handed individuals. We hypothesize that the right hemisphere system is less skilled at controlling variable-rate movements and becomes maximally engaged at a lower movement rate without further modulation. These findings demonstrate that right- and left-hand movements engage different neural systems to control movement, even during a relatively simple thumb flexion task. Specialization of the left hemisphere corticostriatal system for dexterity is reflected in asymmetric mechanisms for movement rate control.

Brain imaging studies examining the component processes of reading using words, non-words, and letter strings frequently report task-related activity in the left extrastriate cortex. Processing of these linguistic materials involves varying degrees of semantic, phonological, and orthographic analysis that are sensitive to individual differences in reading skill and history. In contrast, single letter processing becomes automatized early in life and is not modulated by later linguistic experience to the same degree as are words. In this study, skilled readers attended to different aspects (single letters, symbols, and colors) of an identical stimulus set during separate sessions of functional magnetic resonance imaging (fMRI). Whereas activation in some portions of ventral extrastriate cortex was shared by attention to both alphabetic and non-alphabetic features, a letter-specific area was identified in a portion of left extrastriate cortex (Brodmann's Area 37), lateral to the visual word form area. Our results demonstrate that while minimizing activity related to word-level lexical properties, cortical responses to letter recognition can be isolated from figural and color characteristics of simple stimuli. The practical utility of this finding is discussed in terms of early identification of reading disability.

Children with autism spectrum disorders in very rare cases display surprisingly advanced "hyperlexic" reading skills. Using functional magnetic resonance imaging (fMRI), we studied the neural basis of this precocious reading ability in a 9-year-old hyperlexic boy who reads 6 years in advance of his age. During covert reading, he demonstrated greater activity in the left inferior frontal and superior temporal cortices than both chronological age- and reading age-matched controls. Activity in the right inferior temporal sulcus was greater when compared to reading age-matched controls. These findings suggest that precocious reading is brought about by simultaneously drawing on both left hemisphere phonological and right hemisphere visual systems, reconciling the two prevailing, but seemingly contradictory, single hemisphere theories of hyperlexia. Hyperlexic reading is therefore associated with hyperactivation of the left superior temporal cortex, much in the same way as developmental dyslexia is associated with hypoactivation of this area.

Identification of spatiotemporal interactions within/between neuron populations is critical for detection and characterization of large-scale neuronal interactions underlying perception, cognition, and behavior. Univariate analysis has been employed successfully in many neuroimaging studies. However, univariate analysis does not explicitly test for interactions between distributed areas of activity and is not sensitive to distributed responses across the brain. Multivariate analysis can explicitly test for multiple statistical models, including the designed paradigm, and allows for spatial and temporal model detection. Here, we investigate multivariate analysis approaches that take into consideration the 4D (time and space) covariance structure of the data. Principal component analysis (PCA) and independent component analysis (ICA) are two popular multivariate approaches with distinct mathematical constraints. Common difficulties in using these two different decompositions include the following: classification of the revealed components (task-related signal versus noise), overall signal-to-noise sensitivity, and the relatively low computational efficiency (multivariate analysis requires the entire raw data set and more time for model identification analysis). Using both Monte Carlo simulations and empirical data, we derived and tested the generalized partial least squares (gPLS) framework, which can incorporate both PCA and ICA decompositions with computational efficiency. The gPLS method explicitly incorporates the experimental design to simplify the identification of characteristic spatiotemporal patterns. We performed parametric modeling studies of a blocked-design experiment under various conditions, including background noise distribution, sampling rate, and hemodynamic response delay. We used a randomized grouping approach to manipulate the degrees of freedom of PCA and ICA in gPLS to characterize both paradigm coherent and transient brain responses. Simulation data suggest that in the gPLS framework, PCA mostly outperforms ICA as measured by the receiver operating curves (ROCs) in SNR from 0.01 to 100, the hemodynamic response delays from 0 to 3 TR in fMRI, background noise models of Guassian, sub-Gaussian, and super-Gaussian distributions and the number of observations from 5, 10, to 20 in each block of a six-block experiment. Further, due to selective averaging, the gPLS method performs robustly in low signal-to-noise ratio (<1) experiments. We also tested PCA and ICA using PLS in a simulated event-related fMRI data to show their similar detection. Finally, we tested our gPLS approach on empirical fMRI motor data. Using the randomized grouping method, we are able to identify both transient responses and consistent paradigm/model coherent components in the 10-epoch block design motor fMRI experiment. Overall, studies of synthetic and empirical data suggest that PLS analysis, using PCA decomposition, provides a stable and powerful tool for exploration of fMRI/behavior data.

The complexities of pediatric brain imaging have precluded studies that trace the neural development of cognitive skills acquired during childhood. Using a task that isolates reading-related brain activity and minimizes confounding performance effects, we carried out a cross-sectional functional magnetic resonance imaging (fMRI) study using subjects whose ages ranged from 6 to 22 years. We found that learning to read is associated with two patterns of change in brain activity: increased activity in left-hemisphere middle temporal and inferior frontal gyri and decreased activity in right inferotemporal cortical areas. Activity in the left-posterior superior temporal sulcus of the youngest readers was associated with the maturation of their phonological processing abilities. These findings inform current reading models and provide strong support for Orton's 1925 theory of reading development.